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Enhancing patient diversity in clinical trials has become a key priority in drug development. The main concern is that critical data that includes underrepresented patient populations is being left out as many clinical trials do not reflect all populations that may eventually take a therapy. These underrepresented groups consist of women, including those who are pregnant and lactating, pediatric and elderly patients, people with disabilities, LGBTQ+ individuals, and racial/ethnic groups specifically, Black/African American, American Indian/Alaska Natives, Hispanics/Latinos, Asians, Native Hawaiian, and other Pacific Islanders.
As a result, the U.S. government has taken increased measures with the passage of the Food and Drug Omnibus Report Act of 2022 (FDORA), which will require sponsors to submit diversity plans to the U.S. Food and Drug Administration (FDA) for all late-stage studies with demographic enrollment targets and actionable strategies to reach historically underrepresented racial and ethnic patient groups. While meaningful advancements have been made driving increased industry focus, further collaborative efforts are needed to create sustained impact and improve patient outcomes for all.
To learn more about the latest expectations for enhancing clinical trial diversity, we interviewed Rose Blackburne, MD, MBA, vice president and global head of general medicine and women’s health at the PPD clinical research business of Thermo Fisher Scientific.
In the following interview, Dr. Blackburne discusses the latest regulatory requirements around diversity in clinical trials, how the industry is responding and what actions will help enable further progress in clinical trial health equity in the years ahead.
Setting the stage for clinical trial diversity
Can you talk about the latest efforts by regulatory agencies like FDA to encourage the industry to continue to step up efforts to improve diversity in clinical trials?
Dr. Rose Blackburne
Blackburne: While the FDA has a longstanding commitment to promoting diversity and inclusion in industry trials, heightened expectations have been placed on sponsors and clinical research organizations (CROs) to proactively develop strategies and report back on how they are doing in conducting clinical trials that better serve patients who have been historically underrepresented.
In 2023, the FDA released several new and updated guidances to help direct drug development programs to include underrepresented groups, such as recommendations on approaches to obtaining data on these populations in the post-marketing setting and guidance on the implementation of decentralized clinical trials to help reduce patient burden. Mandated under FDORA, highly anticipated final guidance is expected to be released this year that builds on the 2022 guidance for sponsors on approaches to developing a diversity plan.
While many sponsors have been actively developing and executing diversity strategies, this new mandate requiring sponsors to submit diversity plans at the end of Phase II will help standardize the prioritization of diversity in clinical trials across the industry. Stakeholder accountability also has been underscored, with the FDA set to submit annual reports to the U.S. Congress with aggregated findings on whether clinical studies met their demographic enrollment goals, and reasons why such goals were not met.
Additionally, we are seeing increased measures being taken outside of the US to ensure trials reflect real-world populations. This year, for example, regulatory bodies in the United Kingdom are expected to unveil a proposed approach for inclusion and diversity plans for drug and medical device studies conducted in the region. As part of this effort, a set of questions and supporting guidance are being developed for researchers to consider when they design clinical trials, looking at multiple dimensions of diversity beyond race and ethnicity. I anticipate we will see continued regulatory focus on the inclusion of underrepresented groups in other regions of the world in the years ahead, tailored to how diversity looks and is defined in a particular geography.
Understanding FDA expectations and evolving standards
You were one of many clinical development leaders who spoke at a recent public workshop hosted by the FDA and the Clinical Trials Transformation Initiative (CTTI) to solicit stakeholder input on ways to enhance diversity in clinical studies. What were the highlights from this discussion and do they provide any direction on how expectations for clinical trial sponsors will evolve?
Blackburne: The two-day Food and Drug Omnibus Reform Act of 2022 (FDORA) public workshop included leaders from the FDA, academia, patient advocacy organizations and industry coming together for an in-depth discussion on the importance of establishing clinical study enrollment goals using disease prevalence or incidence data and approaches to remove barriers, while supporting the inclusion of historically underrepresented populations. Notably, the opening and closing statements on both days emphasized that patient diversity is a top priority for the FDA. The discussion also reinforced that clinical trial diversity is a key factor for eliminating health care disparities across diverse populations.
While most discussions on this topic often focuses primarily on inclusion of underrepresented racial and ethnic groups in clinical trials, the FDORA public workshop was a robust dialogue covering barriers and solutions that include not only race and ethnicity, but also other key facets of patient diversity, such as age (pediatric and elderly populations), sexual orientation and gender identity, pregnancy and lactation, developmental and intellectual disabilities, and behavioral health challenges. A holistic, multi-pronged approach to addressing barriers to clinical trial participation among all underrepresented groups affected by a particular disease or condition is paramount to ensuring that drug products and medical devices are tested and found to be safe and effective in all groups that represent real-world populations.
We are already seeing pharmaceutical and device companies broadening the scope of their patient diversity efforts beyond just focusing on one aspect of patient diversity – such as race and ethnicity or gender – and also addressing social demographics that impact health disparities like socioeconomic status. With continued evidence generation in understudied populations and true partnership with these communities, we stand to learn valuable lessons that will change how clinical trials are conducted in the years ahead.
The workshop also further highlighted the view that the FDA’s diversity plan is not about checking a regulatory box. It is a living, iterative strategy that requires sponsors to continuously engage, collaborate and problem-solve with the agency and other stakeholders to yield different results than we’ve historically seen. While the plan requirement currently only extends to Phase III trials or other pivotal trials, sponsors also need to be planning for diversity in early development (e.g., engaging and listening to communities/advocacy groups) to set up future trials for success.
Strategies for success for clinical trial diversity
How are health care organizations responding to ensure they are prepared to meet industry expectations around making clinical trials reflective of real-world patient populations?
Blackburne: At the workshop, the industry was reminded that “what got us here, won’t get us there” in fixing this long-standing issue that continues to negatively impact patient outcomes. There has been actionable progress in rethinking how clinical research is conducted to make it more diverse and inclusive. Enhancing evidence-based medicine is of central importance. The discussion also focused on the importance of properly designed and conducted clinical trials, appropriate primary and secondary endpoints, use of validated biomarkers, randomization to enhance reliability and use of controls with established standard of care measures – all of which are aimed at ensuring evidenced-based generalizability of study results.
First, research professionals must be knowledgeable on the topic of diversity in clinical trials to keep pace with regulatory guidance and expectations1, yet this area of training is often widely unavailable or underutilized. Everyone across the clinical trial life cycle can play a role, but many may not know where to start. To address this, some companies have made progress in embedding an inclusive mindset and solutions that address health care disparities into everyday working practices. For example, our workforce is provided training opportunities and functional-level toolkits to help them recognize the barriers that prevent different populations from participating in clinical trials and feel empowered to act.
Organizations also are dedicating new resources to this issue. Many pharmaceutical companies have created diversity-focused teams and/or cross-functional working groups to address internal and external barriers to clinical trial participation. Similarly, within the PPD clinical research business, we have a team of patient diversity subject matter experts (SMEs) who partner across our business and with customers, research sites and community stakeholders to develop and support sponsor diversity initiatives. With a dedicated SME involved at the study level, we can provide hands-on support to build inclusive strategies early in the study design and work to optimize trial startup and enrollment for the inclusion of historically underrepresented populations. We also partner with community organizations, speak at industry congresses and participate in industry working groups and joint task forces focused on diversity in clinical trials. Examples include the Society for Clinical Research Sites (SCRS), Multi-Regional Clinical Trials Center of Brigham and Women’s Hospital and Harvard (MRCT) and the Association of Clinical Research Organizations (ACRO). These forums provide the opportunity to exchange best practices and ensure clinical researchers are bringing the latest evidence and community-centered thinking to the clinical trials we support.
The workshop emphasized the importance of building trust in diverse communities by cultivating meaningful, sustainable relationships, partnering with trusted organizations, building a community-based diverse clinical research workforce, and embedding research sites and research advocates in the community. There has been initial progress in building the relationships and infrastructure to establish and include more clinical research sites in diverse communities into the research process. Historically, clinical research has been concentrated at academic medical centers and research sites in major cities, creating barriers to access for many underrepresented groups. Meeting industry expectations requires building a pipeline of experienced clinical research sites and providers at the local level with research staff from diverse backgrounds who have built trust in their community. One example of how we’re doing that at our organization is through a collaboration with the National Minority Quality Forum (NMQF) to disrupt the traditional approach to clinical trial recruitment. This collaboration will help build the capacity for U.S. community health clinics to participate in clinical trials through training and connection to sponsor trials.
By evolving working practices and partnering with community sites directly to help them grow, the industry can make trials accessible to a wider range of people while satisfying regulatory and quality standards. Ultimately, we are striving to create a future where patient diversity roles no longer exist because inclusive practices have become a standard component of how all clinical trials are run.
The future of clinical trial diversity
Looking ahead to the next year and beyond, what do you predict will enable further tangible progress in diversity in clinical trials?
Blackburne: “Let’s not wait for Congress to pass additional legislation to move the needle.” This was one of FDA’s main messages in motivating sponsors, CROs, sites and community partners to better collaborate and share experiences that will move the field forward together. Looking ahead, we will soon have collective insights and trends stemming from the diversity plan initiative that will facilitate more transparency and information-sharing about what is working and what is not. It will be our responsibility to adapt to what we learn.
I am optimistic about the future innovation and efficiencies that will come from new technologies, such as artificial intelligence, to help bring more underrepresented groups into the research process. We must, however, be intentional about its use to ensure the demonstrated progress we’ve already made is not trivialized and health disparities are not further perpetuated.
Policy incentives are an important motivator for change. However, it will be up to the industry to continue to experiment and build capabilities to reach underserved populations through the implementation of comprehensive, evidenced-based strategies. Those organizations that are responsive and dedicate significant resources and budget to this issue will be the most effective at accelerating progress going forward.
References
- Niranjan SJ, Durant RW, Wenzel JA, et al. Training Needs of Clinical and Research Professionals to Optimize Minority Recruitment and Retention in Cancer Clinical Trials. Journal of Cancer Education. 2019;34(1):26-34. doi:10.1007/s13187-017-1261-0
Rose Blackburne, MD, MBA, is vice president and global head of general medicine, cardiovascular/metabolic and women’s health at the PPD clinical research business of Thermo Fisher Scientific. In this role, she has strategic input and oversight for a portfolio of pharmaceutical and medical device product development opportunities across therapeutic areas including women’s health, cardio-metabolic diseases, nephrology, dermatology and urology.
Dr. Blackburne is a globally recognized thought leader in health equity and diversity in clinical research. Based in the Washington, DC, area, she is a board-certified physician with over 25 years of experience in health care. She received her medical degree at the Morehouse School of Medicine and completed an Obstetrics and Gynecology residency at Columbia University/Harlem Hospital Center. She holds a Master of Business Administration from the Darden Graduate School of Business at the University of Virginia, studied Health Policy and Health Care Delivery at the Harvard University John F. Kennedy School of Government, and earned her B.A. from the University of Virginia.